This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sivak, A. Articles by Kensler, C. J. Search for Related Content PubMed PubMed Citation Articles by Sivak, A. Articles by Kensler, C. J.

Studies on the Formation of Phthalanilide-Deoxyribonucleic Acid Complexes and Their Relationship to Chemotherapeutic Activity¹

( Life Sciences Division, Arthur D. Little, Inc., Cambridge, Massachusetts)

Complexes between DNA³ and substituted iso- and terephthalanilides occur in dilute aqueous solution and are measured by spectrophotometric methods. There appears to be no specificity among DNA preparations from different sources or different phthalanilides with regard to the stoichiometry of the interaction. The DNA-phthalanilide complex is less affected by heating and cooling than DNA alone. Most of the phthalanilide-DNA complexes examined are partially dissociable at moderate (0.01 M) salt concentrations and completely dissociable in 8 M urea. Poly-L-lysine also causes a dissociation of the complex. However, 1 congener, 4',4''-bis(N'-methylamidino)terephthalanilide, forms a complex with DNA which is stable in 0.1 M CaCl₂ or 0.155 M NaCl.

In general, the phthalanilide-DNA complex appears to be the result of weak ionic forces, with the exception of 4',4''-bis(N'-methylamidino)terephthalanilide. Hydrogen bonding and perhaps hydrophobic bonding are also thought to play a lesser role in the formation of phthalanilide-DNA complexes. The disposition of DNA as a helix or random coil may also affect the interaction.

The interaction between DNA and the phthalanilides in vitro does not appear to be correlated with the therapeutic efficacy of this class of compounds in the treatment of mouse leukemia, although it has not been ruled out as a possible primary site of action in vivo.

¹ These studies were supported by Cancer Chemotherapy National Service Center Contract SA-43-PH-3789, National Cancer Institute, National Institutes of Health.

³ The following abbreviations are used: DNA, deoxyribonucleic acid; RNA, ribonucleic acid.

² Present address: Institute of Environmental Medicine, New York University Medical Center, 550 First Avenue, New York.

Received 7/ 6/64. Revised 3/ 1/65.